For the above reasons, the researchers combined oncolytic virus with a variety of immune checkpoint inhibitors (anti-CTLA-4 antibody, anti-PD-L1/PD-1 antibody, etc.), which can achieve the oncolytic virus and immune cell " Double anti-cancer effect. The RIBAS team first injected melanoma patients with oncolytic virus (talimogene laherparepvee, T-Vee), and then intravenously injected PD-1 inhibitors. The results showed that the patient's CD8* T cells increased, while the PD- expression level of L1 protein has also increased.
In addition, oncolytic viruses can also be used in combination with immunoadjuvants and CAR-T cells in 184 cases. This treatment is usually more effective and safe than monotherapy.
1. Oncolytic virus combined with photodynamic therapy
Photodynamic therapy (PDT) refers to the use of a specific wavelength of laser to excite the photosensitizer, so that the photosensitizer transfers energy to the surrounding oxygen to generate singlet oxygen ('O2), which in turn produces a strong cytotoxic effect. Some researchers believe that the anti-tumor ability of oncolytic viruses can be improved by regulating the tumor vascular endothelial factor signaling pathway. GIL and others used the oncolytic poxvirus combined with PDT to treat primary or metastatic tumors in mice, and found that PDT can destroy tumor blood vessels and enhance the anti-tumor effect of the virus. With the continuous development of oncolytic virus therapy, oncolytic virus combined with PDT therapy has gradually shown the potential of clinical application, or it can be used to treat cancer that cannot be operated or has entered advanced stage. KHALED et al first used reovirus combined with protoporphyrin IX (PpIX)-mediated PDT to act on pancreatic cancer cells, and the combined effect on tumor cells was significantly more lethal than any one of them alone.
2. Oncolytic virus combined with photothermal therapy
It has been reported that the replication of adenovirus is related to the activation of heat shock response, and the uptake of external substances by cells is affected by temperature. Based on the above phenomenon, JUNG and others have proved that gold nanorod (GNR)-mediated photothermal therapy can enhance the transduction efficiency and replication ability of oncolytic adenovirus in head and neck cancer cells, and it has a strong killing effect, and can significantly inhibit the growth of tumors in JHU-022 (oral cancer cell line) tumor animal model.
Oncolytic virus clinical trials
At present, the research of oncolytic viruses is like fire, and many oncolytic viruses have entered the clinical trial stage in succession.
In recent years, oncolytic virus, as a potential anticancer drug, has made significant progress in pre-clinical and clinical research. However, there are some disadvantages in the application of oncolytic viruses. Due to its strong immunogenicity, it is easy to be cleared after entering the body, and it is easy to cause a strong immune response in the body, and finally reach the tumor site to play a tumor suppressing effect. The amount of virus is very small, making oncolytic virus therapy difficult to achieve the desired tumor suppression effect. The use of vectors to load oncolytic viruses, although to a certain extent, has shown many advantages, but it also has some limitations. For example, when using cells to load oncolytic viruses, they may be affected by autologous cells and cell differentiation and development; when using polymers, organic frameworks or inorganic materials to encapsulate viruses, their effectiveness and safety need to be further improved. Later research is expected to discover more powerful and biocompatible materials to build a universal and effective oncolytic virus vector platform, so that the virus can escape the body's immune system without affecting the virus's infectivity surveillance and effective transportation to the tumor site to achieve the site-specific enrichment of the virus, reduce toxic and side effects, maximize the proliferation of oncolytic virus in the tumor site, and achieve the optimal tumor suppression effect. On this basis, the oncolytic virus is combined with other anti-cancer methods, such as radiotherapy, chemotherapy, immunotherapy, etc., carefully select treatment methods and optimize the combination of the two, as far as possible under the premise of ensuring their respective effects. Finally, by improving the safety and effectiveness of the carrier and the oncolytic virus itself, it will show better biocompatibility with the human body, thereby turning more oncolytic viruses into anti-tumor clinical research.

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